The pituitary gland secretes growth hormone (GH) which stimulates growth in body tissues capable of growing and affects metabolic processes by increasing the rate of protein synthesis and decreasing the rate of carbohydrate synthesis in cells. Growth hormone also facilitates the mobilization and use of free fatty acids for energy.
Growth hormone secretion is regulated by two hypothalamic peptides: GH-releasing hormone (GHRH), which exerts a stimulatory effect on GH release, and somatostatin, which exhibits an inhibitory influence. Growth hormone levels can be increased by administering compounds known to induce GH release, such as GHRH. Administration of such growth hormone releasing agents and the resulting increase in the GH level provide important medical and physiological benefits in mammals, including the acceleration of growth, increase of muscular mass, and, with sufficiently high GH levels, enhanced production of milk.
It has been demonstrated that GH secretion can also be stimulated by synthetic oligopeptides termed GH-releasing peptides (GHRP), such as hexarelin and various hexarelin analogs (Ghigo et al., European Journal of Endocrinology, 136, 445–460, 1997). These compounds act through a mechanism which is distinct from that of GHRH (C. Y. Bowers, in “Xenobiotic Growth Hormone Secretagogues”, B. Bercu and R. F. Walker, eds., pp. 9–28, Springer-Verlag, New York 1996) and by interaction with specific receptors localized in the hypothalamus and pituitary gland (G. Muccioli et al., Journal of Endocrinology, 157, 99–106, 1998; G. Muccioli, “Tissue Distribution of GHRP Receptors in Humans”, Abstracts IV European Congress of Endocrinology, Sevilla, Spain, 1998).
Given the importance of growth hormone releasing peptides in veterinary and human medicine as in many commercial applications, there remains a need for growth hormone releasing peptides that are more efficacious than those currently in existence. The present invention addresses this need by providing growth hormone releasing pseudopeptides that are surprisingly found to more effectively stimulate the release of growth hormone than the known GH secretagogues.